Percentage Of Free Testosterone Research Articles

(256) Effect of Early Varicocelectomy Intervention on Male Hormone Levels in Adolescent Males

Abstract Introduction Varicoceles can be found in approximately 15% of the adult male population and are known to impact male fertility. Varicoceles may develop during adolescence and increase in size as these males undergo puberty. According to current guidelines, it is recommended to monitor young asymptomatic patients and consider surgical intervention if they develop testicular size discrepancies, fertility issues, abnormal semen analyses, or experience significant pain. However, the effect of varicoceles on sex hormones and management in young males is poorly understood. Objective To evaluate the impact of early surgical intervention for varicoceles with a microsurgical varicocelectomy on hormone levels and safety profiles in adolescent males. Methods A retrospective review was conducted on 67 patients between the ages of 10 and 17 years old who had a grade 2 (G2) or grade 3 (G3) varicocele, and underwent microsurgical varicocelectomy between November 2021 and May 2023. Patient demographics, varicocele laterality and grade, surgical data, and pre-and post-operative hormone levels were collected as well as post-operative complications. Hormonal panel was collected before 11AM using LCMS and included total testosterone (TT), free testosterone (FT), percent free testosterone (%FT), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (P), and sex hormone-binding globulin (SHBG). Statistical analyses were conducted using SAS System. Results A total of 67 patients had complete data (96% had G3 varicoceles). Preoperative FT was statistically significant between varicocele grades 2 and 3 (p=0.03) with G3 varicoceles having lower preop FT levels. Pre-operative hormone levels for G2 varicoceles were: TT 550ng/dL (std 177ng/dL), FT 126ng/dL (std 27), E2 33 (std 2.64), FSH 3.53 (std 1.27) and LH 5.06 (std 3.53). Pre-op levels for G3 varicoceles: TT 437ng/dL (std 199ng/dL), FT 71.3 (std 42.2), E2 25.2 (std 9.64), FSH 4.34 (std 3.3) and LH 3.73 (std 1.9). Post operatively TT levels improved in G3 varicocelectomy patients with a postop mean TT 445ng/dL (std 109ng/dL), however this did not meet statistical significance. There was no statistically significant difference between postoperative hormone panel labs between varicocele grades. There were no complications in any of the patients and no recurrence of varicoceles. Conclusions Our study evaluated the impact of early surgical intervention for G2 and G3 varicoceles on hormone levels in adolescent males. The results showed a significant difference in preoperative Free T levels between G2 and G3 varicocele patients possibly indicating the impact of varicocele grade on FT levels in adolescents. Early surgical intervention for G3 varicoceles appears to be safe with resultant improvements in TT levels with no increased risk of complications. Further investigations to explore the potential benefits of early surgical treatment in adolescent patients with varicoceles evaluating hormonal profiles in larger cohorts. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast and BK Ultrasound.

Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure.

Free testosterone (FT) determination may be helpful in evaluating men suspected of testosterone deficiency especially in conditions with altered binding-protein concentrations. However, methods for measuring FT by equilibrium dialysis and reference intervals vary among laboratories. To determine reference intervals for FT in healthy, nonobese men by age groups as well as in healthy young men, 19-39 years, using a standardized equilibrium dialysis procedure METHODS: We measured FT in 145 healthy, nonobese men, 19 years or older, using a standardized equilibrium dialysis method performed for 16-h at 37°C using undiluted serum and dialysis buffer that mimicked the ionic composition of human plasma. FT in dialysate was measured using a CDC-certified liquid chromatography tandem mass spectrometry assay. In healthy nonobese men, the 2.5th, 10th, 50th, 90th, and 97.5th percentile values for FT were 66, 91, 141, 240, and 309 pg/ml, respectively; corresponding values for men, 19-39 years, were 120, 128, 190, 274, and 368 pg/ml, respectively. FT levels by age groups exhibit the expected age-related decline. FT levels were negatively associated with body mass index, age, and sex hormone-binding globulin (SHBG) levels. Percent FT was lower in middle-aged and older men than young men adjusting for SHBG level. Further studies are needed to determine how these reference intervals apply to the diagnosis of androgen deficiency in clinical populations and in men of different races and ethnicities in different geographic regions. Reference intervals for free FT levels (normative range 66-309 pg/ml [229-1072 pmol/L] in all men and 120-368 pg/ml [415-1274 pmol/L] in men, 19-39 years), measured using a standardized equilibrium dialysis method in healthy nonobese men, provide a rational basis for categorizing FT levels. These intervals require further validation in other populations, in relation to outcomes, and in randomized trials.

Changes of sex hormones and sex hormone-binding globulin levels in male adults with hyperthyroidism before and after antithyroid drug treatment

Objective: To observe the changes of sex hormone and sex hormone-binding globulin (SHBG) levels in young male patients with hyperthyroidism before and after antithyroid drug (ATD) treatment. Methods: Between January 2015 and July 2016, forty male patients with hyperthyroidism aged 19-52 years (with an median age of 33.1 years) were enrolled in the Department of Endocrinology of Peking Union Medical College Hospital. Blood samples were taken before treatment and at 1 month, 2 months, 3 months and 5 months after treatment to evaluate thyroid function, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone(T), free testosterone(FT), estradiol(E2), prolactin and SHBG. Results: A total of 40 patients were enrolled but only 35 patients completed the follow-up. The patients had high levels of thyroid function, SHBG and sex hormones before treatment. Before treatment, free thyroxine (FT(4)), free triiodothyronine (FT(3)), SHBG, LH, estradiol, testosterone and free testosterone was (0.30±0.12) pmol/L, (9.68±4.73) pmol/L, (146±111) nmol/L, (8.41±3.61) U/L, (19.9±7.7) pmol/L, (29.9±9.5) nmol/L and (0.24±0.08) nmol/L, respectively. After treatment, the level of triiodothyronine, thyroxine, FT(3) and FT(4) gradually decreased to normal (all P<0.001). Thyroid stimulating hormone (TSH) gradually increased to normal (P<0.001). LH and estradiol levels gradually decreased (all P<0.001). FSH decreased but the difference was not statistically significant. Prolactin did not change significantly. Testosterone and SHBG levels decreased significantly while the levels of free testosterone, free testosterone percentage (FT%), bio-available testosterone (BAT), bio-available testosterone percentage (BAT%), free androgen index (FAI) gradually increased and stabilized (all P<0.001). The difference was not statistically significant between T/LH and E2/LH before and after treatment (all P>0.05). However FT/LH gradually increased and its difference was statistically significant (P<0.001). Conclusion: The levels of LH, estradiol, testosterone and SHBG in male patients with hyperthyroidism significantly increased, while the free testosterone level decreased, but they all gradually returned to normal with the lowering of thyroid hormone levels during ATD treatment.

Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes

BackgroundAn ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity. Metabolic flexibility has been explored previously in women with polycystic ovary syndrome (PCOS), yet the independent or synergistic contributions of androgen excess and/or insulin resistance is not yet known. Therefore, the purpose of this article was to characterize metabolic flexibility in women with PCOS compared to women of normal BMI, obesity, or type 2 diabetes (T2DM).MethodsEighty-six weight-stable women; thirty with either PCOS (n = 30), or fifty-six with obesity (n = 12), T2DM (n = 27), or normal BMI (n = 17) underwent a hyperinsulinemic euglycemic clamp and indirect calorimetry to measure insulin sensitivity and substrate oxidation via indirect calorimetry, respectively.ResultsAll analyses were adjusted for differences in age, ethnicity, and BMI between groups. Women with PCOS were less metabolically flexible compared to healthy women with obesity (p < 0.0001), normal BMI (p < 0.0001), but after controlling for glucose disposal rate, were similar to women with T2DM (p = 0.99). When dividing women with PCOS above and below the mean cutoff for insulin resistance, the insulin resistant women with PCOS had lower rates of non-oxidative glucose metabolism (p = 0.0001), higher levels of percent free testosterone (p = 0.04), a higher free androgen index (p = 0.006), more visceral adipose tissue (p = 0.02), and were less metabolically flexible (p = 0.007).ConclusionsWomen with T2DM were as metabolically inflexible as women with PCOS. When stratifying women with PCOS into those who are metabolically flexible and inflexible, the women who are inflexible display greater amounts of visceral fat and androgen excess. The inability to alter substrate use given the physiological stimulus may lead to subsequent increases in adiposity in women with PCOS thereby further worsening the insulin resistance.Trial registration numberClinical Trials.gov, NCT01482286. Registered 30 November 2011.

Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS

PurposeTo determine whether ovarian morphology imaged using transabdominal ultrasonography reflects clinical and metabolic features in adolescents with polycystic ovary syndrome (PCOS). MethodsA retrospective pilot study was conducted in 33 adolescents (12–18 years) with PCOS as defined by hyperandrogenism and irregular cycles. Adolescents underwent the following assessments at a random time during the menstrual cycle: transabdominal ultrasonography, physical examination (height, weight, and systolic and diastolic blood pressure), fasting hormonal tests (free, percent free, and total testosterone, androstenedione, follicle stimulating hormone, luteinizing hormone), and metabolic tests (including an oral glucose tolerance test, fasting and 2-hour insulin and glucose, homeostatic model assessment of insulin resistance, and whole-body insulin sensitivity index). Ultrasound images were analyzed offline for ovarian area (OA), ovarian volume (OV), follicle number per cross section (FNPS), and follicle distribution pattern. Associations among endocrine and metabolic variables with sonographic features were assessed by Spearman's rank correlation coefficients and stepwise multiple linear regression. ResultsTotal testosterone and androstenedione, but not free testosterone, or percent free testosterone, positively correlated with OA (ρ = .515, ρ = .422, respectively), OV (ρ = .451, ρ = .382), and FNPS (ρ = .394, ρ = .474). Luteinizing hormone:follicle stimulating hormone ratio also positively correlated with ovarian size (OA, ρ = .520 and OV, ρ = .409). Unexpectedly, body mass index (ρ = −.503) and fasting glucose levels (ρ = −.393) were inversely correlated with FNPS. Total testosterone was an independent predictor of FNPS, OA, and OV as judged by stepwise multiple regression analyses. ConclusionsSome aspects of ovarian morphology in adolescents with PCOS using transabdominal ultrasonography associate with markers of reproductive dysfunction and provide rationale to further investigate how ovarian morphology may reflect concurrent metabolic dysfunction.

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance

Background: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism. Materials and methods: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase. Results: DHEAS was found to be higher in the nonobese patients as compared to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IR< 2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p = .005). Conclusions: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.

The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure.

To identify relationships between anabolic hormones, inflammatory markers, and physical function. Cross-sectional. Outpatient university heart failure program in Connecticut. Sixty patients with an ejection fraction of 40% or less. The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Linear and ordinal logistic regression analyses were performed for the physical measures. Forty-three men (mean age 77 +/- 9) and 17 women (mean age 78 +/- 12) participated. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) (all P<.05). Percentage of free testosterone, DHEAS alone, and N-terminal pro-brain natriuretic peptide (NTpro-BNP) did not correlate with 6-minute walk distance. Higher frailty phenotype score (more frail) was correlated with higher high-sensitivity CRP, higher IL6, and lower 25OHD levels (all P<.05). Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25OHD, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed age, sex, 25OHD and hsCRP to be significant (coefficient of determination=53.5%). Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that age, 25OHD, and hsCRP also predicted frailty status. Twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

Hypoactive sexual desire disorder in postmenopausal women: is there a relation with hormone replacement therapy and sex steroid hormonal levels?

To investigate whether there is an association between hormone replacement therapy (HRT), serum hormonal levels and the prevalence of Hypoactive Sexual Desire Disorder (HSDD) in postmenopausal women. Cross-sectional study. Women attending outpatient gynecologic clinic completed questionnaires evaluating sexual function. These included the Brief Index of Sexual Functioning, the Profile of Female Sexual Function, and the Personal Distress Scale. The participants' serum levels of estradiol, androgens, and sex hormone binding globulins (SHBG) were determined. The main outcomes measured were the demographics of the interviewees, the impact of hurricane Katrina, HRT use, presence of HSDD, and hormone levels. Student's t, chi-square, and ANOVA tests were used. Odds ratios (OR) were calculated using the Cochran-Mantzel-Haenszel test. An α = 0.05 and a power of 80% were used. All analysis were performed using SAS version 9.0. TableStudy Participants and HRTHRT (n)No HRT (n)Race∗∗ White3524 Non-White411Age 30–49188 50–591622 >6055BMI (Kg/m2)∗∗ 18.5–24.92310 25–29.9610 >30914Katrina PreKatrina76 PostKatrina3229Menopause type∗ Natural1327 Surgical268Clinical history∗ Prior hysterectomy3313 Prior oophorectomy2721HSDD HSDD1714 No HSDD2221∗ P<0.005; ∗∗ P<0.05. Open table in a new tab ∗ P<0.005; ∗∗ P<0.05. Seventy five menopausal women, ages 32 to 66 years, were recruited from two clinics in New Orleans and Houma. HRT use was more common in women who were White (60% vs. 27% in non-Whites, P=0.049), younger than 50, had oophorectomies (69% vs. 31%, P=0.0002), had a hysterectomy (85% vs.15%, P<0.0001), or had a normal body mass index (BMI) (59% vs.15% in overweight and 23% in obese, P=0.029). The majority of women on HRT were using estrogen alone (ERT) (84%). ERT users had a significantly higher SHBG (P<0.05). They also had a higher estradiol level and a lower percent free testosterone, although not statistically different. The use of HRT was not associated with HSDD (OR = 1.16; CI 0.46–2.93). Furthermore there were no differences in hormone levels among women affected with HSDD. This study confirms that HSDD cannot be correlated to sex hormone levels and is not affected by HRT use. Although they had a higher SHBG, ERT users did not have a higher prevalence of HSDD. The elevated SHBG level, which is associated with a lower bioactive androgen, seems to be counterbalanced by an elevated estradiol that has a positive impact on the vagina. This reflects the multifactorial etiology of sexual dysfunction.

ORIGINAL RESEARCH—ENDOCRINOLOGY: Wide Variability in Laboratory Reference Values for Serum Testosterone

The laboratory determination of testosterone levels consistent with a diagnosis of hypogonadism is complicated by the availability of multiple testosterone assays and varying reference ranges. To assess current laboratory practices regarding availability of testosterone assays and use of reference values. A telephone survey of 12 academic, 12 community medical laboratories, and one national laboratory. Types of androgen assays offered and determination of reference values. All of the academic and eight of the community centers performed total testosterone testing. Free testosterone was performed in-house by six of the 12 academic and one community center. Testing for bioavailable testosterone, free androgen index, and percent free testosterone was performed in-house by no more than two centers. There were eight and four different assays used for total and free testosterone, respectively. One national laboratory offered equilibrium dialysis measurement of free testosterone. Of the 25 labs, there were 17 and 13 different sets of reference values for total and free testosterone, respectively. The low reference value for total testosterone ranged from 130 to 450 ng/dL (350% difference), and the upper value ranged from 486 to 1,593 ng/dL (325% difference). Age-adjusted reference values were applied in four centers for total testosterone and in seven labs for free testosterone. All reference values were based on a standard statistical model without regard for clinical aspects of hypogonadism. Twenty-three of the 25 lab directors responded that clinically relevant testosterone reference ranges would be preferable to current standards. Laboratory reference values for testosterone vary widely, and are established without clinical considerations.

The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD) on overweight and obese women with PCOS.ResultsEleven women with a body mass index >27 kg/m2 and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%), percent free testosterone (-22%), LH/FSH ratio (-36%), and fasting insulin (-54%). There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems.ConclusionIn this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period.

Clinical and metabolic findings in adolescent females with hyperandrogenism

BackgroundThe purpose of this study was to characterize the population of adolescent females with laboratory evidence of hyperandrogenism and to explore clinical and laboratory features that may facilitate the diagnosis and management of this condition. We further investigated these characteristics by race, weight, and type of androgen abnormality. MethodsA 4-year retrospective chart review was undertaken. Female patients were included if they attended Adolescent Medicine Clinic and had at least one abnormal laboratory parameter on a testing panel that included total and free testosterone, calculated percent free testosterone, and sex hormone binding globulin levels. ResultsOur final sample included 154 females, 70% of whom were white, 28% African-American and 2% of other ethnicities. The mean age was 16.1 years (range 11–23). The mean body mass index (BMI) was 30.4, ranging from 16.6 to 45.0, and 78% were obese (BMI>95th percentile for age). Initial reason for visit included irregular menses in 75.3%, acne or hirsutism in 7.1%, and other reason in 17.5%. Non-whites were more likely than whites to present with other reason for visit (28 vs. 13%, P<0.05). Non-white patients had a higher chronologic and gynecologic age at presentation than whites. Total testosterone was elevated in 82.6% of the non-white compared to 62.0% of the white patient group (P<0.05). There was no difference in BMI or obesity between whites and non-whites. The subgroup of adolescents with an isolated elevated testosterone was leaner, had a younger gynecologic age, and was more likely to have an abnormal glucose to insulin ratio than were those girls with other androgen abnormalities. Of those tested for other metabolic abnormalities, 55% had at least one abnormal lipid value, and 68% had an abnormal glucose to insulin ratio. ConclusionsAdolescent females with hyperandrogenism are at risk for other metabolic abnormalities. The higher gynecologic age and higher testosterone levels in our non-white patient group may reflect a delay in referral. Primary care physicians need to be sensitive to signs and symptoms of hyperandrogenism in the non-white population and in lean adolescents.

Differential Effects of Oral Estrogen Versus Oral Estrogen-Androgen Replacement Therapy on Body Composition in Postmenopausal Women

A decrease in lean body mass and increased fat characterize menopause, related to both aging and likely decreased hormone secretion. Estrogen/androgen (E/A) treatment not only relieves vasomotor symptoms in menopausal women but demonstrably reduces fat mass while increasing lean body mass. This 16-week, double-blind trial randomly assigned 40 postmenopausal women (mean age 57 years) to receive either esterified estrogen alone (Estratab) in a dose of 1.25 mg daily (E group) or E/A therapy in the form of esterified estrogen plus 2.5 mg daily of methyltestosterone. The 37 women completing the study all had received estrogen for 3 months or longer. A double-dummy design was used to blind the study medication. In addition to anthropometric measurements, bone density was measured by dual-energy x-ray densitometry at the spine, hip, and forearm. The same technique provided estimates of fat mass, percentage of fat tissue, and lean body mass of the trunk and extremities. Muscle strength was estimated by weight lifting. The two treatment groups were demographically comparable. E/A treatment increased lean body mass in the trunk and extremities significantly more than estrogen alone. Body fat percentage declined significantly in the E/A group only. The difference between groups was significant for lean body mass and percentage of fat tissue when analyzing changes in the arms, legs, and trunk simultaneously. Body weight increased with E/A treatment by 2.7 pounds on average, and skin-fold thickness decreased. Upper- and lower-body strength increased with E/A treatment. Lower-body strength did not increase significantly with estrogen alone. Serum estradiol levels increased similarly in the two groups after 16 weeks. Percentage of free testosterone increased more in the E/A group, and luteinizing hormone and sex hormone-binding globulin values decreased significantly more in this group than in women given estrogen alone. Women given E/A therapy had significant reductions in total and high-density lipoprotein cholesterol and triglycerides, with no substantial change in low-density lipoprotein cholesterol. Low-density lipoprotein cholesterol fell significantly in the estrogen-only group. Several measures of sexual function demonstrated increases in frequency of sex, pleasure, and orgasms in women given E/A treatment. Changes were significantly more marked than in the estrogen group. Women in both groups exhibited an improved quality of life in several domains, including cognition, anxiety, depression, and vasomotor/sleep problems. Three women withdrew because of side effects, but no clinically significant liver dysfunction was observed. Postmenopausal women in good general health gained an improved body composition in this trial after 4 months of estrogen/androgen therapy. Muscle strength also improved, and these women seemed to have an improved quality of life and better sexual function compared with those given estrogen alone.

Hormone profiles in humans experiencing military survival training

Background: Clinical models of the human response to intense, acute stress have been limited to laboratory settings or cross sectional characterizations. As a result, data about the sensitivity of the human neuroendocrine activation to realistic stressors of varying magnitudes are limited. The U.S. Army survival course offers a unique opportunity to examine, in a controlled manner, the human response to acute, realistic, military stress. Methods: Salivary data were collected in 109 subjects at baseline during four stress exposure time points and at recovery. Serum data was collected at baseline and recovery in 72 subjects and at baseline and during stress exposure in a subgroup of subjects ( n = 21). Results: Cortisol significantly increased during the captivity experience and was greatest after subjects’ exposure to interrogations. Cortisol remained significantly elevated at recovery. Testosterone was significantly reduced within 12 hours of captivity. Reductions of both total and free T4 and of total and free T3 were observed, as were increases in thyrotropin. Conclusions: The stress of military survival training produced dramatic alterations in cortisol, percent free cortisol, testosterone, and thyroid indices. Different types of stressors had varying effects on the neuroendocrine indices. The degree of neuroendocrine changes observed may have significant implications for subsequent responses to stress.

The analog free testosterone assay: are the results in men clinically useful?

Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or "bioavailable" testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0.62; P <0.01). In contrast, in women serum concentrations of total testosterone (r = -0.26; P = 0.17), free testosterone (r = -0.30; P = 0.17), and BAT (r = -0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5-0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.

INFLUENCE OF RADICAL PROSTATECTOMY ON SERUM HORMONE LEVELS

Purpose The influence of radical prostatectomy on the hypothalamic pituitary axis has not been well studied. It is also unclear how alterations in serum androgen levels that result from surgical removal of the prostate might influence the recovery of libido and sexual function following radical prostatectomy. We determined the influence of radical prostatectomy on the hypothalamic pituitary testicular axis of 63 men with clinically localized prostate cancer treated only with radical prostatectomy. Materials and Methods A total of 63 healthy men 43 to 67 years old were enrolled in this prospective study. Phlebotomy was performed immediately before and 1 year following radical retropubic prostatectomy. Sera were stored frozen and analyzed as a group at the end of the study. We measured serum testosterone, percent free testosterone, dihydrotestosterone (DHT), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin and prolactin. Results Following radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone, estradiol, LH and FSH (p <0.0001), and statistically significant decrease in serum DHT (p <0.0001). No difference was noted in serum sex hormone binding globulin or prolactin levels. There was no statistically significant correlation between any serum hormone and sample storage time, patient age or prostate volume that could limit potential bias in study design. Serum hormone changes did not correlate with pathological stage or histological grade for this group of patients. Conclusions Radical prostatectomy influences the hypothalamic pituitary axis by increasing serum testosterone, percent free testosterone, estradiol, LH and FSH while decreasing serum DHT levels. These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion. Further investigation is warranted to identify this substance or substances.

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

Relationship of leptin concentration to gender, menopause, age, diabetes, and fat mass in African Americans.

This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34.2 +/- 7.4 years), 29 age-matched premenopausal women (mean age, 32.6 +/- 3.7 years), and 36 postmenopausal women (mean age, 57.8 +/- 5.9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (p=0.04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0.001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7.51 +/- 8.5, 33.9 +/- 17.3, 31.4 +/- 22.3 ng/mL. Leptin/FM x 100 in the three groups were: 28.9 +/- 16.1, 98.65 +/- 44.9, 77.1 +/- 44.5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0.001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0.83, p<0.001), in premenopausal women it was FM only (R=0.57, p<0.001), and in postmenopausal women it was weight only (R=0.67, p<0.001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.

Visceral adiposity, androgens, and plasma lipids in obese men

The primary purpose of this study was to investigate the relationships between adipose tissue (AT) distribution, particularly visceral adipose tissue (VAT), circulating androgens, and plasma lipids in a group of 17 obese (body mass index [kg/m 2], 31.8 ± 3.8) android (waist to hip ratio [WHR], 1.01 ± 0.05) men. AT distribution was measured by magnetic resonance imaging (MRI) using a multislice model in which 41 equidistant images were acquired from head to foot. Although the subjects were homogenous with respect to total adiposity, a sevenfold variation in VAT was observed. VAT and the visceral to subcutaneous ratio (VSR) were significantly correlated with triglyceride (TG) levels and the ratio of apolipoprotein (apo) B to low-density lipoprotein cholesterol ([LDL-C] P < .05). Neither proximal-thigh AT area nor lower-body subcutaneous adipose tissue (SAT) volume was significantly related to any lipid variable. However, the ratio of visceral AT area to thigh AT area (VTH) was positively correlated with TG ( P < .05), and the ratio of VAT volume to lower-body SAT volume (VLBS) was positively correlated with TG, total cholesterol (TC), LDL-C ( P < .05), and apo B ( P = .057). Total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) were not significantly related to any of the plasma lipid variables; however, the percentage of FT (%FT) was positively correlated with high-density lipoprotein cholesterol ([HDL-C] P < .01) and HDL-C/LDL-C ( P < .05). TT, FT, %FT, and SHBG were not related to MRI-measured VAT. Age was not related to either VAT or androgen levels. The observed relationships between VAT, androgens, and plasma lipids were similar regardless of whether VAT was determined using a single abdominal image (cm 2) or a combination of seven abdominal images (cm 3). Furthermore, the segmentation of intraperitoneal (IP) AT from VAT did not affect the observed relationships. The findings of this study suggest that in obese android men, absolute and relative measures of visceral adiposity are stronger correlates of plasma lipid variables than are circulating androgens.

Two Different Pathogenetic Mechanisms May Play a Role in Acne and in Hirsutism

Summary OBJECTIVE Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandro-sterone and its sulphate, testosterone) and target tissue-produced androgens (testosterone and its 5α-reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation. DESIGN AND PATIENTS To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out-patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne. Twenty-four women without acne or hirsutism and without a history of endocrine disease were studied as controls. MEASUREMENTS In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3α-androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated. RESULTS Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3α-androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels. CONCLUSIONS Our results demonstrate that dihydrotestosterone is further reduced to 3α-androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotesterone itself. Moreover, our results demonstrate that 3α-androstanediol and its glucuronide cannot be used as plasma markers of target-tissue produced androgens in all hyperandrogenic conditions.

Free testosterone and abortion in early pregnancy

OBJECTIVES: To investigate the relationship between percentage of free testosterone (% free T) and the abortion rate in early pregnancy. METHODS: Progesterone (P), estradiol (E2), total T, sex hormone binding globulin (SHBG), and % free T were measured in sera obtained from 60 pregnant women with normal pregnancy (n = 38) and missed abortion (n = 22) at between 4 and 12 weeks' gestation. RESULTS: P, E 2, total T, and SHBG in 22 patients with missed abortion were significantly lower than those in normal group, whereas % free T was significantly higher. There was a significant negative correlation between % free T and SHBG concentration in the normal group, but not in the missed abortion group. All the subjects in whom % free T was 1.30% and higher subsequently miscarried, but no subject with % free T less than 0.70% had a miscarriage. CONCLUSIONS: The lower the % free T, the lower the rate of subsequent abortion. The value of % free T may be able to predict pregnancy outcome in early pregnancy.